Disorders of blood cells may begin in the biological environment where the cells develop, not just with the cells themselves, according to a study from researchers at the Massachusetts General Hospital (MGH) and the Peter MacCallum Cancer Center (Peter Mac) in Melbourne, Australia.
In the June 15 issue of Cell, the investigators describe finding that genetic alterations in the bone marrow of mice can cause a type of myeloproliferative syndrome, an overproduction of certain blood cells that also occurs in human patients.
"Previously all myeloproliferative syndromes have been considered to be intrinsic to the blood cells themselves," says Louise Purton, PhD, of the MGH Center for Regenerative Medicine, formerly of Peter Mac, who led the study. "This discovery may help us find better therapies for these disorders, which can be quite difficult to treat, and also for some leukemias."
How the bone marrow microenvironment contributes to the development and maintenance of blood cells has been the subject of intense research interest in recent years. In 2003 MGH researchers found that the bone-forming osteoblasts that line the marrow cavity can regulate the production of hematopoietic (blood system) stem cells. Although it is known that certain blood disorders can affect this microenvironment, the induction of a blood-cell disease by environmental factors alone has not been reported previously.
Purton's team has been studying how a group of vitamin A receptor molecules regulate hematopoietic stem cell (HSC) production and previously showed that the RAR-gamma receptor was critical to HSC renewal. In that work they observed that mice in which RAR-gamma had been knocked out had significantly fewer HSCs and increased numbers of more mature progenitor cells.